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Gene | BRAF |
Variant | V600E/K |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF V600E/K indicates a mutation that results in the replacement of the valine (V) at amino acid 600 of the Braf protein by either a glutamate (E) or lysine (K). V600E/K mutations are hotspot mutations in Braf that result in increased Braf kinase activity (PMID: 15035987). |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF V600E/K BRAF mutant BRAF V600X BRAF V600E/K |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF V600E/K PIK3CA wild-type | melanoma | sensitive | Selumetinib + Vemurafenib | Preclinical | Actionable | In a preclinical study, Selumetinib (AZD6244) and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). | 26137449 |
BRAF V600E/K PIK3CA wild-type | melanoma | sensitive | Dactolisib + Vemurafenib | Preclinical | Actionable | In a preclinical study, BEZ235 and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). | 26137449 |
BRAF V600E/K PIK3CA wild-type | melanoma | sensitive | Vemurafenib + ZSTK474 | Preclinical | Actionable | In a preclinical study, ZSTK474 and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). | 26137449 |
BRAF V600E/K PIK3CA wild-type | melanoma | sensitive | Selumetinib + ZSTK474 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Selumetinib (AZD6244) and ZSTK474 combination treatment inhibited proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture, and synergistically inhibited tumor growth in cell line xenograft models (PMID: 26137449). | 26137449 |
BRAF V600E/K PIK3CA wild-type | melanoma | sensitive | Dactolisib + Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Koselugo (selumetinib) and BEZ235 combination treatment inhibited proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture, and synergistically inhibited tumor growth in cell line xenograft models (PMID: 26137449). | 26137449 |
BRAF V600E/K PIK3CA wild-type | melanoma | no benefit | A66 | Preclinical | Actionable | In a preclinical study, A66 did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). | 26137449 |
BRAF V600E/K PIK3CA wild-type | melanoma | no benefit | TGX-221 | Preclinical | Actionable | In a preclinical study, TGX-221 did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). | 26137449 |
BRAF V600E/K PIK3CA wild-type | melanoma | no benefit | Idelalisib | Preclinical | Actionable | In a preclinical study, Zydelig (idelalisib) did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). | 26137449 |
BRAF V600E/K PTEN loss | Advanced Solid Tumor | predicted - sensitive | PX-866 + Vemurafenib | Phase I | Actionable | In a Phase I trial, the combination therapy of PX-866 and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response in 28% (5/18) of advanced solid tumor patients harboring BRAF V600E or K, and of those five patients, 80% (4/5) also demonstrated loss of PTEN (PMID: 29051322). | 29051322 |
BRAF V600E/K CDKN2A loss RB1 pos | melanoma | predicted - sensitive | Palbociclib + Vemurafenib | Phase Ib/II | Actionable | In a phase I/II trial, Ibrance (palbociclib) plus Zelboraf (vemurafenib) was safe and resulted in an overall response rate (ORR) of 26.7% (4/15), disease control rate (DCR) of 80% (12/15), and progression-free survival (PFS) of 2.8 mo in metastatic melanoma patients with prior BRAF inhibitor treatment and BRAF V600E/K, CDKN2A loss, and RB1 expression, and an ORR of 27.8% (5/18), DCR of 83.3% (10/18) and 2.8 mo PFS when combined with pts without prior BRAF inhibitor treatment (PMID: 33947696; NCT02202200). | 33947696 |